1. There is no "one size fits all" solution; there is no magic bullet. What works for me will not necessarily work for you. What works for you will not necessarily work for Jim. You need to really look at both the logistics and the potential impact of any promotion efforts before you commit to them, because you only get so many shots. Which leads us to...
2. You only get so many shots. You have how many opportunities to make a first impression? Right. One. Assume that the average reader who is interested in your genre and could possibly be convinced to give you a second glance is willing to give you as many as four opportunities to be impressive. This is a very, very generous estimate; most readers will give you one shot, maybe two, because there is a lot of stuff out there to read. So if you run three unsolicited BUY MY BOOK BUY MY BOOK BUY MY BOOK Twitter campaigns, you only have one more chance to reach that reader. That unimpressed reader.
3. Most people don't like junk mail. Don't be junk mail. I can literally count on the fingers of one hand the number of times I've received something in the mail that I didn't ask for, looked at it, and gone "oooo, yes, I want this thing." Well, if you send me a bulk email without my having asked for it, you're in that mailbox. Does it work sometimes? Yeah. Send 1,000 emails, sell three books. But you've potentially just associated yourself, however wrongly, with the word "spammer" in 997 readers' heads.
4. Be appropriate to the venue. Let's say Olga wrote a book. And let's say she's been thinking a lot about promotion. She sees this article. She sees people talking about promotion, and books, and hey, that Seanan girl's a writer, right? All her commenters must be readers! So Olga goes around and replies to every single comment with "let me tell you about my book." Olga has now been inappropriate to the venue, and odds are she's gathered very few sales.
5. Building a brand is more vital than flogging a single book. I love the cover to Discount Armageddon, almost as much as I love the book itself. It's exactly what I wanted. Some others were not so impressed, since it was the first portrayal of a sexualized character on one of my books (and so PINK!). Many of them bought the book anyway. Why? Because I have built my brand, and they knew they could trust me. Sometimes the sales of book one will not rock your world. But they'll increase awareness for book two, and that can be vital.
6. Do not put yourself in a box. There are a thousand ways to promote yourself without resorting to junk mail and thread-jacking. Buy ad space on popular web comics. Do guest blogs. Send review copies to book bloggers you trust. Sign up for things like Scalzi's Big Idea. Don't just go "oh, I found the one way, I'm good." That way lies madness.
7. You will never have all the readers. It is not possible, barring your becoming the next Stephen King or Stephanie Meyer, for you to have name-recognition with all the readers, much less be read by all the readers. Even King and Meyer don't have all the readers. Maybe people don't read them. It's just that many more people do. Don't freak out about the ones who won't read you, they were never going to read you anyway.
8. It does not end. Yesterday, I emailed a reviewer that I know isn't on any of my lists and asked if she wanted a copy of Ashes of Honor. Today, I will give away two ARCs. Tomorrow, I will go to a convention. Promo never ends, and if you think it does, you're going to be very sad.
9. Choose sincerity. You can't just do things with the photo op in mind; you have to do them because you want to, because they're the right thing, because they're fun or awesome or somehow make you happy. That's promo, too. The ripple effect works.
10. Once someone says stop, you need to stop. The number of times I've seen an author permanently alienate a reader or group of readers by continuing a) to barrage them with promo, and b) explain their brilliant idea is...bad. It's definitely not good. Now, I am not saying "do not blog about your book." Your blog is YOUR SPACE, and anyone who's going to get pissed at you for talking about something that is a huge chunk of your life in YOUR SPACE is a jerk and you don't need them. But if you follow me around Facebook trying to explain your genius, we're not going to be besties.
There. Those are my helpful hints. Now if you'll excuse me, I'm going to go spelunking in a whale carcass.